• James C Hogg, John E McDonough, Pablo G Sanchez, Joel D Cooper, Harvey O Coxson, William M Elliott, David Naiman, Marcus Pochettino, Debra Horng, Warren B Gefter, and Alex C Wright.
• Emeritus Lab Medicine, iCAPTURE Center, St Paul's Hospital, Vancouver, BC V6Z 1Y6, Canada. jhogg@mrl.ubc.ca
• Proc Am Thorac Soc. 2009 Sep 15; 6 (6): 546-9.

BackgroundThe smaller airways, < 2 mm in diameter, offer little resistance in normal lungs, but become the major site of obstruction in chronic obstructive pulmonary disease (COPD).ObjectiveTo examine bronchiolar remodeling and alveolar destruction in COPD using micro-computed tomography (micro-CT).MethodsMicro-CT was used to measure the number and cross-sectional lumen area of terminal bronchioles (TB) and alveolar mean linear intercept (Lm) in 4 lungs removed from patients with very severe (GOLD-4) COPD and 4 unused donor lungs that served as controls. These lungs were inflated with air to a transpulmonary pressure (P(L)) of 30 cm H(2)O and held at P(L) 10 cm H(2)O while they were frozen solid in liquid nitrogen vapor. A high resolution CT scan was performed on the frozen specimen prior to cutting it into 2-cm thick transverse slices. Representative core samples of lung tissue 2 cm long and 1 cm in diameter cut from each slice were fixed at -80 degrees C in a 1% solution of gluteraldehyde in pure acetone, post-fixed in osmium, critically point dried, and examined by micro-CT.ResultsA 10-fold reduction in terminal bronchiolar number and a 100-fold reduction in their minimal cross-sectional lumen area were measured in both emphysematous and non-emphysematous regions of the COPD lungs.ConclusionsThe centrilobular emphysematous phenotype of COPD is associated with narrowing and obliteration of the terminal bronchioles that begins prior to the onset of emphysematous destruction.

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